The incidence rate of liver cancer has been rising in recent years. Traditional cell line culture and human patient-derived tumor xenograft models, which are commonly used tools to simulate the occurrence of human liver cancer, have deepened the understanding of tumor occurrence, development, and drug resistance mechanisms. However, they cannot reflect the accurate state of cancer cells, the tumor microenvironment, or spatial structural characteristics. Recently, more in vitro-produced physiological liver organoids have been applied in the study of liver cancer. Liver organoid models have made breakthroughs in the occurrence and development mechanisms of liver cancer, personalized drug screening and biomarker identification, immunotherapy, and regenerative medicine applications. This paper mainly summarizes the progress and application of liver organoids processed in the study of liver cancer.

Objective:To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies.Methods:In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups.Results:The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2=5.442, P<0.001). HER-2 and Epstein–Barr virus positivity rates did not differ significantly between the two groups. Conclusion:Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

OBJECTIVE To provide reference for improving the dispensing accuracy of similar drugs and reducing dispensing error risk through exploring the dispensing mode of similar drugs. METHODS The effectiveness and feasibility of the similar drug dispensing management mode was explored through adjusting the traditional horizontal or vertical sorting method to a “Z” shaped cargo location sorting， implementing similar drug in different zones dispensed by different people， and combining measures such as adjusting the format of drug dispensing documents and improving inventory methods. The role of similar drug dispensing mode in drug dispensing management was evaluated comprehensively from two aspects： work quality and work efficiency. RESULTS After the implementation of similar drug dispensing mode， total number of monthly dispensing errors （18.42±8.79 vs. 28.50±6.87，P= 0.005） and the proportion of monthly dispensing errors of similar drugs （[ 4.17±5.71）% vs. （10.96±7.05）%，P＝0.017] were significantly lower than before the implementation； the monthly consistency rate between accounts and materials （[ 98.46±0.73）% vs. （97.61±0.57）%， P＝0.004] was significantly higher than before implementation； completion time of dispensing in each batch was not significantly affected， and daily work was carried out smoothly and orderly. CONCLUSIONS The similar drug dispensing mode has a significant effect in improving the accuracy of dispensing similar drugs， reducing the risk of dispensing errors， and does not affect the efficiency of dispensing work.

Objective:To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies.Methods:In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups.Results:The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2=5.442, P<0.001). HER-2 and Epstein–Barr virus positivity rates did not differ significantly between the two groups. Conclusion:Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

Objective::Dopamine, via its receptors, plays a vital role in the maintenance of blood pressure by modulating renal sodium transport. However, the role of the D 4 dopamine receptor (D 4 receptor) in renal proximal tubules (PRTs) is still unclear. This study aimed to verify the hypothesis that activation of D 4 receptor directly inhibits the activity of the Na +-K +-ATPase (NKA) in RPT cells. Methods::NKA activity, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were measured in RPT cells treated with the D 4 receptor agonist PD168077 and/or the D 4 receptor antagonist L745870, the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). Total D 4 receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Results::Activation of D 4 receptors with PD168077, inhibited NKA activity in RPT cells from WKY rats in a concentration- and time-dependent manner. The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D 4 receptor antagonist L745870, which by itself had no effect. The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ, which by themselves had no effect on NKA activity, eliminated the inhibitory effect of PD168077 on NKA activity. Activation of D 4 receptors also increased NO levels in the culture medium and cGMP levels in RPT cells. However, the inhibitory effect of D 4 receptors on NKA activity was absent in RPT cells from SHRs, which could be related to decreased plasma membrane expression of D 4 receptors in SHR RPT cells. Conclusions::Activation of D 4 receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs. Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.

Objective::Dopamine, via its receptors, plays a vital role in the maintenance of blood pressure by modulating renal sodium transport. However, the role of the D 4 dopamine receptor (D 4 receptor) in renal proximal tubules (PRTs) is still unclear. This study aimed to verify the hypothesis that activation of D 4 receptor directly inhibits the activity of the Na +-K +-ATPase (NKA) in RPT cells. Methods::NKA activity, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were measured in RPT cells treated with the D 4 receptor agonist PD168077 and/or the D 4 receptor antagonist L745870, the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). Total D 4 receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Results::Activation of D 4 receptors with PD168077, inhibited NKA activity in RPT cells from WKY rats in a concentration- and time-dependent manner. The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D 4 receptor antagonist L745870, which by itself had no effect. The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ, which by themselves had no effect on NKA activity, eliminated the inhibitory effect of PD168077 on NKA activity. Activation of D 4 receptors also increased NO levels in the culture medium and cGMP levels in RPT cells. However, the inhibitory effect of D 4 receptors on NKA activity was absent in RPT cells from SHRs, which could be related to decreased plasma membrane expression of D 4 receptors in SHR RPT cells. Conclusions::Activation of D 4 receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs. Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.

Objective: To explore the effects of oxidative stress on renal dopamine D₁ receptor dysfunction in offspring of diabetic rat dams. Methods: The pregnant Sprague Dawley (SD) rats (n=10) were randomly divided into the diabetic group (a single intraperitoneal injection of 35 mg/kg streptozotocin on day 0 of gestation) and control group (injected with the equal volume of 0.9% saline on day 0 of gestation) according to the random number table (n=5 each group). The offspring rats were divided into 4 groups including offspring of control dams treated with vehicle, offspring of control dams treated with antioxidant, offspring of diabetic dams treated with vehicle and offspring of diabetic dams treated with antioxidant (n=10 each group). After birth, the offspring rats were treated with normal drinking water or antioxidant (tempol, 1.0 mmol/L) from the age of 4 weeks until the end of the study (20 weeks). The blood pressure was monitored continuously by non-invasive tail-cuff method. The renal oxidative markers including superoxide dismutase (SOD) and malondialdehyde (MDA) activity and D₁ receptor agonist (fenoldopam)-mediated urinary and sodium excretion were detected. Furthermore, the protein expression of renal G protein-coupled receptor kinase 2 (GRK2), GRK4, dopamine D₁ receptor and the phosphorylation level of D₁ receptor were detected. Results: The mean arterial pressure of offspring from the diabetic dams treated with vehicle was significantly higher than that of offspring from control dams treated with vehicle (P=0.013), while the mean arterial pressure of offspring from diabetic dams treated with antioxidant was significantly lower than that of offspring from the diabetic dams treated with vehicle (P=0.038). The fenoldopam-mediated urinary flow and urinary sodium excretion rate were significantly lower in offspring of diabetic dams treated with vehicle than those in offspring of control dams treated with vehicle (P<0.01), which were significantly higher in offspring of diabetic dams treated with antioxidant as compared to offspring of diabetic dams treated with vehicle (both P<0.01). There was no significant difference in fenoldopam-mediated urinary flow and urinary sodium excretion rate in offspring of control dams treated with antioxidant or vehicle (urinary flow: P=0.772; urinary sodium excretion rate: P=0.716). Compared with offspring of control dams treated with vehicle, the renal MDA activity was significantly increased, while the SOD activity was significantly decreased in offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.013). The renal MDA activity was significantly decreased, while the SOD activity was significantly increased in offspring of diabetic dams treated with antioxidant in comparison with offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.035).The renal GRK2 and GRK4 protein expression in offspring of diabetic dams treated with vehicle were significantly higher than those in offspring of control dams treated with vehicle (P<0.01), while the expression levels of renal GRK2 and GRK4 in offspring of diabetic dams treated with antioxidant were significantly downregulated compared with offspring of diabetic dams treated with vehicle (P<0.01). There was no significant difference in the protein expression of dopamine D₁ receptor among 4 groups (P=0.735). The level of dopamine D₁ receptor phosphorylation in offspring of diabetic dams treated with vehicle was significantly higher than that in offspring of control dams treated with vehicle (P<0.01), while the dopamine D₁ receptor phosphorylation level was significantly lower in offspring of diabetic dams treated with antioxidant compared to that in offspring of diabetic dams treated with vehicle (P<0.01). Conclusion Oxidative stress is involved in the dopamine D₁ receptors dysfunction in the offspring of diabetic dams.

Brachythrapy is a technique to implant radioactive isotype into or near tumors.The obvious properties of brachytherapy are a very high dose distribution of center,and rapid dose attenuation with the increasing of distance.Brachytherapy generally includes three major categories:low dose rate,high dose rate and pulse dose rate.The most significant clinical value of brachytherapy is that it could create dose distribution to tumor tissues,but decreased radiation injury of normal tissues close to tumor.The development of the clinical brachytherapy technique is always involved in the radiobiological characteristics.The basic concepts involving clinical brachytherapy radiobiology mainly includes:dose-rate effect,repair of radiation injury,re-oxygenation,cell cycle redistribution and repopulation.An amount of translational medical approach is needed to guide the application of clinical brachytherapy by exploring the interaction between brachytherapy radiobiology and clinical brachytherapy effect,as well as taking advantage of brachytherapy radiobiological characteristics.The ultimate goal is to improve tumor local control rate,reduce the occurrence of adverse reactions,and improve patients' overall survival.

Objective To discuss the dosimetric advantage of computed tomography-guided interstitial brachytherapy compared with the conventional intracavitary brachytherapy for locally advanced cervical cancer,offering a more advantageous clinical treatment approach. Methods Twenty-eight locally advanced cervical cancer patients with bulky tumors ( tumor size>5 cm) after external beam radiotherapy received computed tomography-guided interstitial brachytherapy. Dosimetric outcomes of the current study, including the total dose ( external beam radiotherapy+ brachytherapy ) D90 for the HR-CTV and D2cc for the bladder,rectum, and sigmoid, were compared with a former patient group consisting of 30 patients who received the conventional intracavitary brachytherapy ( uterine tandem+ ovoid pairs ) . Results The mean D90 value for HR-CTV in the intracavitary brachytherapy group and interstitial brachytherapy group were (76.9±5. 7) and ( 88.1± 3. 3) Gy, respectively. The D2cc for the bladder, rectum, and sigmoid in the intracavitary brachytherapy group and interstitial brachytherapy group were (84.7±6. 8) Gy,(69.2±4. 2) Gy,(67.8±4. 5) Gy and (81.8±6. 5) Gy,(6.8±4. 0) Gy,(64.8±4. 1) Gy,respectively.1-year local tumor control rate in the intracavitary brachytherapy group and interstitial brachytherapy group were 59. 3％ and 85. 2％, respectively. Conclusions CT-guided interstitial brachytherapy shows a significant dosimetric advantage compared with the conventional intracavitary brachytherapy, and is, thereby, clinically possible feasible. However,the long term curative effect and toxicity need to be further investigated.